This study is part of an ongoing collaborative effort between researchers at the University of Texas Health Science Center at San Antonio (UTHSCSA), Research Imaging Center (RIC), and the Southwest National Primate Research Center (SNPRC) at the Southwest Foundation for Biomedical Research (SFBR) to develop a neurophysiological and neuroimaging model of photosensitive, generalized epilepsy in the baboon. Interest in this model was sparked by electroclinical similarities between the natural epilepsy of the baboon and juvenile myoclonic epilepsy in humans. Because of ethical considerations regarding seizure provocation by intermittent light stimulation (ILS) and invasive evaluation of idiopathic generalized epilepsies in humans, the baboon model presents a unique opportunity to study the mechanisms underlying photosensitive, generalized epilepsy. A recent pilot study comparing cerebral blood flow (CBF) changes using H215O-PET between photosensitive, epileptic (PS) baboons and nonphotosensitive, asymptomatic (CTL) baboons during ILS has already yielded intriguing data. PS animals demonstrated activation of extrastriatal regions during ILS, especially in the sensorimotor cortices, right anterior cingulate and orbitofrontal regions, areas that were deactivated in the CTL baboons. In the resting state, PS baboons showed significant correlation of parietotemporal CBF with interictal discharge rate. Because of the widespread regional deactivations and activations it is essential to understand the relationships of these regional CBF in the context of connectivity. Two important windows into the epileptic networks include the primary visual and motor cortices. In this study, we intend to evaluate connectivity of visual and motor cortices using H215O-PET using ILS and transcranial magnetic stimulation (TMS), respectively, in order to understand the pathways underlying the regional activations. Covariance of regional CBF changes due to variation ILS frequency and TMS rates will allow modeling structural equation modeling of the networks underlying photosensitivity. Intracranial electrode implantation and electrophysiological monitoring will provide insight into the mechanisms underlying the CBF changes and provide temporal information to evalaute to spike coherence and propagation through the nodes of the epileptic ciruit. Our long- term goal is to unravel the networks not only involved in photosensitivity, but also in the generation and propagation of spontaneously occurring interictal and ictal discharges. The correlation of CBF changes and electrophysiological events will promote the development of a noninvasive neuroimaging model to test the effects of novel antiepileptic medications and target regions with neurostimulation. With these data, we will also be well-positioned to seek additional funding for more detailed electrophysiological and pathological evaluation of potential cortical generators of generalized epilepsy. PUBLIC HEALTH RELEVANCE: The baboon provides a unique animal model to study the mechanisms underlying photosensitive, generalized epilepsy. We propose to correlate neuroimaging findings with electrophysiological monitoring with intracranially implanted electrodes to identify networks involved in the generation and propagation of seizures, whether spontaneous or activated with visual stimuli. This study will lay the foundation for testing new medical or surgical therapies for generalized epilepsy in humans.